In Deinococcus radiodurans and other resistant bacteria, a mechanistic link exists between resistance, manganese accumulation, and protein protection. We previously demonstrated that ultrafiltered, protein-free preparations of D. radiodurans cell extracts prevent protein oxidation at massive doses of ionizing radiation. The two key protective components of the extract were peptides/amino acids and manganese. This year we continued and completed a systematic study of the contribution of each of the 20 common amino acids to protection of enzymes from inactivation, in the presence or absence of manganese. The aromatic and sulfur-containing amino acids were far superior to all others in providing protection. Manganese increased protection, but the effect was minor in comparison to the effect of the amino acid alone. The enzymes studied included those which have a known manganese binding site, those with a binding site for a divalent cation other than manganese, and those with no metal binding sites. Those without metal binding sites were not protected by manganese.